March 16, 2016
By Mark Terry, BioSpace.com Breaking News Staff
Indianapolis-based Eli Lilly and Company announced yesterday that it was changing the primary endpoint of its EXPEDITION3 clinical trial, a Phase III study of solanezumab for Alzheimer’s disease.
Originally, the study had two primary endpoints, cognition and function. The company has shifted its priorities, with the primary endpoint being cognition, with function, based on changes in metrics related to Activities of Daily Living (ADL), being a secondary endpoint. Eli Lilly assured investors that although the change effects data analysis, it doesn’t affect anything else in the study.
“Lilly understands that regulators globally will continue to view both cognitive and functional endpoints as necessary for clinical trials in people with mild Alzheimer’s dementia,” the company stated, “and regulatory guidance has been to include these as co-primary endpoints. Lilly is submitting the EXPEDITION3 amendment to all appropriate regulatory authorities.”
Eli Lilly didn’t take the news terribly well, although it’s been down recently anyway. Shares traded on April 27, 2015 for $70.89, rose to $89.98 on Sept. 17, 2015, then dropped to $76.98 on Oct. 22, 2015. Shares rebounded to $86.20 on Dec. 30, then dropped to $71.42 on Feb. 11, 2016. Shares traded on March 11 at $74.65 and are currently trading for $72.23. After the announcement, they dropped to $71.15, but have recovered slightly.
Cognitive decline, which largely involves memory lapses and forgetfulness, show up early in Alzheimer’s patients. The functional impairment that affects tasks like dressing and cooking associated with Alzheimer’s typically comes later.
Tim Anderson, an analyst with Sanford C. Bernstein & Co., told BloombergBusiness that the change in the study’s focus might make it easier for Eli Lilly to identify whether the drug is showing any benefit. That’s the upside. The downside is it also suggests the company is concerned there may be no improvement in functional activities.
“Regulatory agencies will likely require Alzheimer’s disease drugs to demonstrate both cognitive and functional changes to gain full approval, so on its surface this move by the company is concerning,” said Anderson. “However, as there is no firmly established regulatory pathway for disease-modifying Alzheimer’s disease drugs, our belief is that regulators will maintain flexibility.”
Anderson also points out that if solanezumab is found to be effective, it would be the first disease-modifying drug for Alzheimer’s, which would potentially double the company’s stock price. On the other hand, if it fails, he indicates shares could drop 15 percent. Even a modestly effective Alzheimer’s drug is likely to bring in billions of dollars in sales.
Solanezumab is a monoclonal antibody that binds to soluble monomeric forms of amyloid beta shortly after it is produced. This appears to help clear the brain of amyloid beta before it sticks together in clumps and forms amyloid plaques, which have been identified in the brains of Alzheimer’s patients.
EXPEDITION3 completed enrollment in 2015 and the final patient visit is scheduled for October 2016.
Vamil Divan, an analyst with Credit Suisse, told ABC News that the change in the study’s data analysis plan made investors worried about “what was already a high-risk program.” But given that the drug is being developed for early-Alzheimer’s, which is more marked by forgetfulness rather than functional decline, it makes a certain amount of sense, and that he sees a “path for the drug making it to the market.”
